Foley catheter containing cholesterol

ABSTRACT

The incorporation of cholesterol in natural rubber Foley catheters results in an improved resistance to urinary salt calcification.

1 51 Sept. 24, 1974 FOLEY CATHETER CONTAINING CHOLESTEROL [75] Inventor: Paul C. Adlaf, Park Ridge, 111.

[73] Assignee: The Kendall Company, Walpole,

Mass.

22 Filed: Feb. 12,1973

21 Appl.No.:331,771

[52] US. Cl. 128/349 R, 117/139 [51] Int. Cl A6lm 25/00 [58] Field of Search 128/348, 349 R, 350 R,

[56] References Cited UNITED STATES PATENTS 2,096,296 10/1937 Fromm 128/349 R X OTHER PUBLICATIONS Remington Pharmacological Sciences 1965, pp. l417l423.

Primary ExaminerDalton L. Truluck Attorney, Agent, or Firm-Ellen P. Trevors [5 7 ABSTRACT The incorporation of cholesterol in natural rubber Foley catheters results in an improved resistance to urinary salt calcification.

2 Claims, N0 Drawings 1 FOLEY CATHETER CONTAINING CHOLESTEROL This invention relates to a natural rubber urinary catheter having cholesterol incorporated therein. More particularly, this invention relates to improving the resistance of rubber Foley catheters to urinary salt calcification during long-term catheterizations.

Rubber Foley catheters have been used for many years in urethral catheterizations. However, continuous long-term catheterizations are often unsuccessful because of the severity of urinary salt deposits (calculus) which adhere to the outside and luminal surfaces of the rubber Foley catheter. Consequently, because recatheterizations become necessary, the attendant risks of urinary tract infection and tissue irritation are maximized.

In order to minimize the buildup of calculus and allow long-term catheterization to become a reality, catheters manufactured entirely of a plastic material such as disclosed in US. Pat. Nos. 3,528,869; 3,539,674 and 3,544,668 were developed. Another approach was to apply a surface layer coating of an elastomeric silicone material such as dimethylpolysiloxane to natural rubber catheters. This process and catheter are more fully described in US. Pat. No. 3,434,869. Although some plastic and coated natural rubber catheters are reasonably effective in minimizing calculus buildup, they lack the resiliency and superior handling characteristics of catheters made of natural rubber which urologists traditionally prefer.

Now it has been found that an anti-calcification property is conferred on an indwelling rubber urinary catheter by incorporating cholesterol into the rubber matrix, which constitutes the substance of the catheter, without impairing the essential properties of the natural rubber. The cholesterol can be incorporated throughout the entire catheter but for the purpose of this invention, must be incorporated in at least that portion of the shaft intended for insertion into the body cavity.

For the purpose of this invention, it is not necessary that the cholesterol be incorporated in a homogeneous manner. For example, while it is not desired to be bound by theory, there appears to be a migration of the incorporated cholesterol to the surfaces of the catheter after incorporation. Therefore, it is intended to include a coating of cholesterol on the natural rubber catheter surfaces within the scope of this invention.

More specifically, cholesterol can be incorporated into the rubber matrix by any convenient method, for example, by stirring a slurry of cholesterol in water into the natural rubber latex prior to manufacture or by impregnating the finished catheter by immersing in a solution of cholesterol in a rubber-swelling solvent. By rubber-swelling solvent is meant an organic solvent for which rubber has a natural affinity and, upon immersion, causes the rubber to expand.

More in detail in the latter process mentioned above, the catheter is immersed in the solution for a period of time sufficient to impart the desired percentage of cholesterol to the rubber. After the immersion period, the rubber-swelling solvent is removed by conventional drying techniques.

Some rubber-swelling solvents which can be employed in this process are benzene, chloroform, xylene, carbon tetrachloride or methylene chloride. Generally, an immersion of from -20 minutes in a 5-l0 percent (w/v) of cholesterol in a dry, pure, rubber-swelling so]- amount of rubber extractables in certain instances.

vent is sufficient to impregnate a rubber catheter with from 2-20 percent by weight cholesterol. which concentrations have proven to be effective in reducing calculus buildup. By the term (w/v) is meant a weighed amount of solute per ml. of solution, as in this instance 5-10 grams of cholesterol per 100 ml. of solution. A range of lO-l2 percent by weight cholesterol in the rubber matrix is considered optimum. As previously indicated, the cholesterol must be present in at least that portion of the shaft intended for insertion into the body cavity.

As mentioned above, the percentage of cholesterol incorporated into the rubber matrix is controlled by the concentration of cholesterol in the rubber-swelling solvent and the time the catheter is immersed therein. To obtain the optimum range of cholesterol in the rubber matrix (IO-l2 percent), an immersion time of 45 minutes in a 5 percent solution of cholesterol in benzene is generally sufficient. Although the mechanism of how cholesterol limits the buildup of calculus is not com pletely understood, it is hypothesized that it provides unfavorable sites for the deposit of urinary salts.

The procedures employed for demonstrating the efficacy of this invention and a comparison of tissue irritation between treated and untreated catheters are set forth in the following examples.

EXAMPLE 1 Previously weighed 12 French rubber Foley catheters were set into glass tubes, each tube being 50 cm. in length and having a 14 mm. inside diameter, so that the Y or fork of the catheter rested on the lip of the tube. A 5.0 percent solution (w/v) of cholesterol in benzene was added to each tube so that the desired length of catheter shaft would be immersed. (For these experiments, at least that length of shaft which would be inserted into the body cavity of the test animal was immersed.) The catheter shafts were left immersed for varying lengths of time, removed from the impregnating solution, dried in air overnight at room temperature and then dried under vacuum (0.1 mmHg) to remove the benzene. The catheters were then weighed again and the percent cholesterol in the impregnated portion of the shaft was calculated, taking into account the (The varying conditions and percentages of impregnant for each catheter are reported in Table I.)

These cholesterol impregnated catheters were then used to catheterize white, male rabbits. After 7 days of catheterization, the animals were sacrificed and the catheters removed without deflation, dried in air at room temperature for at least 2 days and the relative calcification of each catheter was scored visually using the following scale:

0 n5 anteaterJamar; iET'iiii T l light calcification 2 moderate calcification 3 severe calcification Separate evaluations for the balloon and shaft areas were performed and then a composite evaluation of the TABLE I Percent by Weight Cholesterol in Time Time in lmpregnated Portion Length Immersed vacuo Calculus Scores Sample of Catheter lmpregnated Minutes (Hrs.) Composite Lumen 1 Not Calculated 9 cm. I20 Unknown 2 l 2 11.1 25 cm. 90 52 0 3 12.2 25 cm. 90 52 0 1 4 15.5 25 cm. 90 120 0 0 5 16.3 25 cm. 90 120 1 1 6 14.7 25 cm. 90 120 0 0 7 14.3 25 cm. 90 120 0 0 8 14.4 25 cm. 90 120 1 3 9 13.0 25 cm. 60 96 1 1 10 12.6 25 cm. 60 96 1 1 11 l2.8 25 cm. 60 96 0 0 12 12.7 25 em. 60 96 0 1 13 13.0 25 cm. 60 96 0 1 14 16.3 15 cm. 60 95 1 2 15 16.7 15 cm. 60 95 1 1 16 4.7 25 em. 10 72 1 1 17 4.8 25 em. 15 72 0 0 18 5.7 25 cm. 20 72 0 0 EXAMPLE 2 Using a 5 percent by weight solution of cholesterol in chloroform, the previously described impregnation process and rabbit catherizations were repeated with another group of rubber Foley catheters. (The conditions, percentages of impregnant and relative evaluations are reported in Table II.)

TABLE 11 Percent by Weight Cholesterol Time Time in in Impregnated Length Immersed vacuo Calculus Scores Sample Portion of Catheter Impregnated Minutes (Hrs) Composite Lumen 1 2.4 25 cm. 5 72 0 0 2 3.4 25 cm. 7 72 l l 3 5.1 25 cm. 10 72 1 1 4 7.7 25 cm. 20 72 0 1 5 8.6 25 cm. 25 72 1 l 6 10.0 25 cm. 72 1 1 7 15.2 20 cm. 60 192 1 3 8 12.5 20 cm. 60 192 2 2 9 13.2 20 cm. 60 192 2 1 [(1 II.() 20 cm. (10 I92 3 2 11 15.8 25 cm. 60 96 0 0 II 15.5 25 cm. 60 96 0 I 13 15.9 25 cm. 60 96 2 2 14 15.9 25 cm. 60 96 3 3 15 18.6 15 cm. 60 95 3 3 lo 19.] 15 cm. 60 95 3 3 Controls m TABLE IIT- Continued Thirty-two 12 French regular, untreated Rubber Control Catheters Foley catheters were used as controls. These control Calculus Scores catheters were also used to cathetenze whlte, male rabbits for 7 days and also evaluated according to the pre- Sample Composite Lumen viously described relative evaluation procedure (the results are given in Table III). C6 3 Observed C7 3 Not Observed C8 2 Not Observed TABLE III c9 2 NOI Observed C10 2 Not Observed Cl 1 I Not Observed Control Catheters C12 0 Not Observed Cl3 l l Calculus Scores CM 2 2 C15 2 2 Sample Composite Lumen C16 3 2 C17 3 3 Cl 3 Not Observed C18 3 3 c2 3 N0! Observed C19 3 3 c3 3 Not Observed C20 3 3 c4 3 Not Observed C21 3 3 c5 3 N6: Observed C22 3 3 5 6 TAB LE Ill Continued fibroblastic reaction only '1 1 leucocytic reaction and fibroblastic tissue 2 fibroblastic reaction and slight leucocytic reaction around Control Catheters implant within capsule C. I I S 3 fibroblastic and moderate leucocytic reaction around implant Cu soles 5 within capsule 4 z Sample Composite Lumen gtiilimtrallzggurliacuon md Intense reaction around implant C23 1 3 The resulting scores were averaged and compared as C24 3 fOllOWSZ C28 3 2 impregnated Control C29 3 3 C30 3 3 No. of Observations 27 24 C31 3 3 Average 1 5.1)., 2.2 r 0.8 2.2 r 1.0 C32 3 3 l 5 Score averages and standard deviations were com- It is readily pp from examination of these puted for each group, i.e. impregnated from benzene, scores that no greater tissue irritation is caused by the impregnated from chloroform and the controls. (These cholesterol impregnated catheters than by the unimresults are tabulated in Table IV.) 20 pregnated controls.

TABLE IV impregnated impregnated Total from from impregnated Benzene Chloroform Controls (z=34) (2:18) (2=l6) z=32) Average Scores Composite 091 Composite 0.51 Composite 1.4 Composite 2.6

Lumen 1.14 Lumen 0.78 Lumen 1.6 Lumen 2.5

Standard Deviation Composite 10.97 Composite 10.62 Composite $1.1 Composite $0.8

Lumen $0.99 Lumen i081 Lumen -1.0 Lumen :0.7

Based on 21 Observed Catheters.

I Histological Evaluation What is claimed is:

Separate histological evaluation were performed 35 A unnary Catheter of Foley type comPl'lsmg an using nine cholesterol impregnated (12 French) cathe- 'f tubtllar Shaft of natural Tubber hav1ng y ters and eight control (12 French) catheters which Insertion P0111011 at one end thereof, 531d y were free of cholesterol. Three separate one-half inch tlon portion havlng incorporated therem 2.0 to 20.0 segments of each catheter were implanted subcutanepercent by weight cholesterol. ously in the back of a rabbit for 7 days, then removed 40 2. The catheter of claim 1 wherein said body inserand scored individually. The scoring was based on mition portion has incorporated therein 10.0 to 12.0 percroscopic histological examination using the following cent by weight cholesterol. l l= l 

2. The catheter of claim 1 wherein said body insertion portion has incorporated therein 10.0 to 12.0 percent by weight cholesterol. 